Thromboxane A 2 Modulates de novo Synthesis of Adrenal Corticosterone in Mice via p38/14-3-3γ/StAR Signaling.

Autor: Yan S; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China.; Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, Massachusetts, 02115, USA., Wang Y; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China., Wang B; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China., Zuo S; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China.; Department of Biopharmaceutics, Tianjin Key Laboratory of Technologies Enabling Development of Clinical Therapeutics and Diagnostics, School of Pharmacy, Tianjin Medical University, Tianjin, 300070, P. R. China., Yu Y; Department of Pharmacology, Tianjin Key Laboratory of Inflammatory Biology, State Key Laboratory of Experimental Hematology, Key Laboratory of Immune Microenvironment and Disease (Ministry of Education), The Province and Ministry Co-sponsored Collaborative Innovation Center for Medical Epigenetics, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, 300070, P. R. China.
Jazyk: angličtina
Zdroj: Advanced science (Weinheim, Baden-Wurttemberg, Germany) [Adv Sci (Weinh)] 2024 May; Vol. 11 (18), pp. e2307926. Date of Electronic Publication: 2024 Mar 09.
DOI: 10.1002/advs.202307926
Abstrakt: Prostanoids are endogenous lipid bioactive mediators that play essential roles in physiological processes such as glucocorticoid secretion. Here, it is found that the thromboxane (Tx)A 2 receptor (TP) is highly expressed in the adrenal cortex of mice. Both global and adrenocortical-specific deletion of the TP receptor lead to increased adiposity in mice by elevating corticosterone synthesis. Mechanistically, the TP receptor deletion increases the phosphorylation of steroidogenic acute regulatory protein (StAR) and corticosterone synthesis in adrenal cortical cells by suppressing p-p38-mediated phosphorylation of 14-3-3γ adapter protein at S71. The activation of the p38 in the adrenal cortical cells by forced expression of the MKK6EE gene attenuates hypercortisolism in TP-deficient mice. These observations suggest that the TxA 2 /TP signaling regulates adrenal corticosterone homeostasis independent of the hypothalamic-pituitary-adrenal axis and the TP receptor may serve as a promising therapeutic target for hypercortisolism.
(© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje